A Review of Liver Function Tests. James Gray Gastroenterology Vancouver

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1 A Review of Liver Function Tests James Gray Gastroenterology Vancouver

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

3 Liver Tests Blood Radiology Histology

4 Consider the Situation Liver disease suspected History Symptoms Signs Incidental finding

5 Consider Risk Factors for Liver Disease High risk behaviours Travel Medications Systemic illnesses Autoimmune disorders Exposures Family history

6 Consider Symptoms of Liver Disease Jaundice Abdominal pain (esp RUQ) Fevers and chills Pruritus Fatigue

7 Consider Physical Findings of Liver Disease Indicators of chronic liver disease: Spider nevi, palmar erythema, gynecomastia, parotid enlargement, muscle wasting Indicators of complications of liver disease: Liver failure Asterixus, encephalopathy, bleeding, bruising Portal hypertension Ascites, caput medussa, esophageal varices

8 Consider physical findings that explain liver disease Right heart failure Malignant lymphadenopathy

9 Probability of an Abnormal Screening Test Result Number of tests done Probability of abnormal result (%)

10 Liver Blood Tests Hepatocellular injury AST, ALT Cholestasis Alk Phos, GGT Liver function INR, Albumin Disease specific markers Viral, iron saturation, ceruloplasmin, auto-antibodies (LDH not specific and not useful as marker of liver disease) Bilirubin does not distinguish hepatitis, cholestasis, hemolysis ALT more specific for liver injury than AST Alk phos found in liver, bone, placenta, intestine, kidney

11 Hepatocytes Bile Ducts ALT, AST Bilirubin Alk Phos, GGT Hepatocellular / Mixed / Cholestatic

12 Hepatocellular Injury Hepatitis AST (SGOT) ALT (SGPT) AST:ALT ratio >2:1 suggests alcohol Mild elevation (<5 times normal) Moderate Severe (>15 times normal)

13 Mild Elevation AST or ALT Chronic viral hepatitis Medications Fatty infiltration Alcohol Autoimmune (esp women) Hemochromatosis Celiac Non-hepatic (hemolysis, myopathy)

14 Drug-Induced Liver Injury (DILI) 10% all adverse drug reactions (most cited reason for drug withdrawal) 30% with acute hepatitis Presentation Subclinical Acute hepatitis Acute cholestasis Chronic liver disease

15 Commonly Implicated Drugs Antibiotics Antiepilectics NSAIDs Statins Anti-TB therapy Anti-retrovirals Cancer chemotherapy

16 Severe ALT or AST Elevations Acute viral hepatitis Medications or toxins Ischemia Autoimmune Acute bile duct obstruction

17 Giannini. CMAJ 2005; 172: 367

18 Time Course and Pattern of Change

19 Approach to Elevated AST or ALT Clues from Hx and Px Check viral serologies, ferritin and iron saturation In absence of symptoms or decompensation: observe, stop alcohol and meds, repeat liver chem in 3-6 mos Persistently abnormal: consider ANA, ttg Ab, ceruloplasmin, alpha1- antitrypsin, liver biopsy

20 Viral Hepatitis Hepatitis A acute, not chronic Hepatitis B acute and chronic Hepatitis C chronic but rarely acute Hepatitis D rare and only with Hep B Hepatitis E similar to Hep A Others EBV, CMV

21 Viral Hepatitis Testing Acute infection IgM Hep A Ab Hep Bs Ag Hep C RNA Chronic infection IgG Hep A (to confirm immunity) Hep Bs Ag, Hep Bc Ab, Hep Bs Ab, Hep Be Ag, Hep B DNA, Hep Be Ab Hep C Ab

22 Immunity Anti-HAV Anti-HBsAb

23 Acute Hep B Infection Chronic Hep B Infection

24 Elevated AST or ALT History and physical Review meds and alcohol Hep A, B, C serology Ferritin, iron saturation + Hep A IgM Observe Observe Negative and Assymptomatic Repeat chem in 3-6 mos Stop alcohol and meds Negative Symptomatic ANA, anti-smooth muscle Ab, ceruloplasmin, alpha1-antitrypsin, Ultrasound + Hep BsAg or Hep C Serial chem for 6 mos Iron sat>50%, Ferritin Genetic markers Liver Biopsy Phlebotomy

25 Cholestasis Extrahepatic Choledocholithiasis Malignancy Chronic pancreatitis Benign strictures Intrahepatic Drugs Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis (PSC)

26 Cholestasis (Bile duct obstruction) Alkaline phosphatase Mostly from liver but also bone and placenta Use GGT to confirm biliary origin (GGT alone is not useful as a screening test) Ultrasound Normal, mass lesions, dilated ducts EUS (ERCP) (Anti-mitochondrial Ab) (Liver biopsy)

27 Elevated Alkaline Phosphatase Hepatobiliary Extrahepatic bile duct obstruction Intrahepatic bile duct obstruction Infiltration Medications Sclerosing cholangitis (esp Inflam bowel dis) Primary biliary cirrhosis (esp women) Nonhepatic Bone, placenta

28 Elevated Alk Phos Confirm liver origin with GGT Abd Ultrasound Dilated bile ducts Normal Ducts ERCP or MRCP Review medications Anti-mitochondrial Ab Liver biopsy Observation

29 Mixed Picture Hepatitis or Cholestasis? Define dominant abnormality if mixed pictures Beware early rise in AST or ALT with acute duct obstruction Follow to define dominant trend

30 True Liver Function Tests INR Albumin (half-life = days)

31 US CT MRI Liver morphology Masses Blood vessels Bile ducts Extrahepatic findings CT-Angio MR-Angio Angiography Imaging EUS MRCP HIDA PTC Blood vessels Portal vein Blood vessel intervention Bile ducts Biliary intervention

32 Special Tests (Disease Specific markers) Viral markers Serum ethanol Fe saturation/ferritin Ceruloplasmin, 24hr urine copper Autoimmune markers (ANA, AMA ) Alpha fetoprotein (Hepatocellular Ca) Abdominal Ultrasound, CT Liver biopsy ERCP / MRCP Elastography (Fibroscan)

33 Hemochromatosis Genetic testing Heterozygote 10% Homozygote 0.5% Check iron saturation (ferritin) Liver biopsy

34 Fatty Liver Hepatic steatosis Non-alcoholic steatohepatitis (NASH)

35 Accuracy of Imaging in Identifying Hepatic Steatosis Compared with Liver Biopsy Eur Radiol 2011; 21: 87

36 Isolated Elevation Bilirubin Isolated unconjugated (indirect) elevation of bilirubin Gilbert s syndrome 5% population Benign condition Hemolysis

37 Isolated elevation of GGT Alcohol NAFLD ( fatty liver ) Enzyme-inducing drugs Infiltrative disorders Often seen with no predisposing conditions and normal liver histology Usually can reassure and follow

38 Monitoring for Complications In face of advanced liver disease (cirrhosis): Hepatocellular carcinoma Abd US q6months Varices Endoscopic screening for varices

39 Summary Abnormal Liver Chemistry Symptomatic or incidental History or physical indicates liver disease Hepatitis or cholestasis Significant or non significant Infectious or non infectious Familial, autoimmune, meds, alcohol Isolated abnormality (eg. GGT, bilirubin)

40 Summary Abnormal Liver Chemistry Consider simple observation and F/U Modify meds, avoid alcohol Specific markers for hepatitis including viral, iron, autoimmune, copper Ultrasound if cholestasis Consider liver biopsy if diagnosis unclear

41 References Abnormal liver chemistry. Viral hepatitis testing. Drug induced liver injury. Gut 2017; 66: 1154 Evaluation of abnormal liver chemistry. Am J Gastro 2017; 112: 18 Use of liver imaging and biopsy in clinical practice. NEJM 2017; 377; 756

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